Characterization of Nicotine-Induced Desensitization of Evoked Dopamine Release from Rat Striatal Synaptosomes
Version of Record online: 23 NOV 2002
Journal of Neurochemistry
Volume 63, Issue 2, pages 561–569, August 1994
How to Cite
Rowell, P. P. and Hillebrand, J. A. (1994), Characterization of Nicotine-Induced Desensitization of Evoked Dopamine Release from Rat Striatal Synaptosomes. Journal of Neurochemistry, 63: 561–569. doi: 10.1046/j.1471-4159.1994.63020561.x
- Issue online: 23 NOV 2002
- Version of Record online: 23 NOV 2002
- Received October 26, 1993; revised manuscript received January 4, 1994; accepted January 4, 1994.
- Nicotinic receptors
Abstract: Nicotine has been shown to stimulate neurotransmitter release from brain tissue by acting on presynaptic receptors. In this study, the ability of nicotine pretreatment to produce functional desensitization was investigated in rat striatal synaptosomes in which the release of [3H]dopamine was measured with an in vitro superfusion system. Pretreatment of synaptosomes with low concentrations of l-nicotine resulted in a decrease in the ability of a subsequent nicotine challenge to evoke [3H]dopamine release. The IC50 for nicotine-induced desensitization was found to be 12 nM with a maximum inhibition of >90% at 300 nM. Nicotine pretreatment did not affect the release evoked by amphetamine, veratridine, or 15 mM K+. The onset of nicotine-induced desensitization occurred with a t1/2 of 43 s at 30 nM nicotine. The temperature dependence of onset yielded a Q10 of 1.2.Recovery from desensitization was slower (t1/2 = 4.33 min), and both the onset and recovery appeared to follow a single first-order process. Several intermittent schedules of nicotine treatment were found to be effective at inducing and maintaining desensitization. The results of this study show that nonstimulating concentrations of nicotine can produce a complete functional desensitization of subsequent nicotine-induced neurotransmitter release.